Chromosomes and genomes, are generally believed to be organized in three dimensions such that functionally related genomic elements, e.g. silencers and enhancers and their target genes, are directly interacting or are located far away from each other.
Genomes are believed to be complex and are composed of nucleic acids and proteins as well as some other biological components.
The activity of genes is tightly regulated to achieve biological functions at the right time and place. Each gene carries a region called promoter, which is a short DNA sequence responsible for interpreting the signals in the cellular environment to decide whether the gene should be activated or not. Specific proteins (transcription factors) bind to the promoter sequence to initiate assembly or disassembly of the protein machinery to either activate or inactivate its gene. Both secondary as well as the tertiary conformational structures of the genomes as well as the regulatory elements constitute the architecture that initiate and directs the events that occurs within a cell. Event that could give rise to different diseases or disorders, or just be normal activities within the cell.
The technology developed by Lieberman-Aiden et al., 2009 (Chromosome conformation capture methodology (Hi-C)) have been used to map long-range interactions and which probes the three dimensional architecture of whole genomes.
Van Berkum L et al., 2010, J. Vis. Exp. Vol 39, el1869doi:10.3791/1869 discloses the conventional Hi-C technology, which could be coupled to other techniques. However, so far all the techniques have had some draw backs and been very time consuming as well as most techniques have a very low resolution.
The new invented technique give rise to a significantly higher mapping of promoters and enhancers compared to other techniques (see example 2 in the application).
However, there are some limitations with the Hi-C technology, including that there is a need to sequence very deep to be able to resolve regulatory interactions between promoter and enhancer elements and thus the Hi-C technology is time consuming as well as expensive and there is a need of developing new techniques that can solve those problems and enable the possibility to evaluate and detect direct intra- and inter-chromosomal interactions between remote regulatory elements, and utilize the information to diagnose specific medical and/or biological conditions.